Amy K. Dumas

Perfluorochemical (PFC) Exposure in Children: Associations with Impaired Response Inhibition

BACKGROUND Perfluorinated chemicals (PFCs) have been used widely in consumer products since the 1950s and are currently found at detectable levels in the blood of humans and animals across the globe. In stark contrast to this widespread exposure to PFCs, there is relatively little research on potential adverse health effects of exposure to these chemicals. OBJECTIVES We performed this cross-sectional study to determine if specific blood PFC levels are associated with impaired response inhibition in children. METHODS Blood levels of 11 PFCs were measured in children (N = 83) and 6 PFCs: perfluorooctane sulfonate (PFOS), perfluorohexane sulfate (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctanesulfonamide (PFOSA), and perfluorodecanoic acid (PFDA) - were found at detectable levels in most children (87.5% or greater had detectable levels). These levels were analyzed in relation to the differential reinforcement of low rates of responding (DRL) task. This task rewards delays between responses (i.e., longer inter-response times; IRTs) and therefore constitutes a measure of response inhibition. RESULTS Higher levels of blood PFOS, PFNA, PFDA, PFHxS, and PFOSA were associated with significantly shorter IRTs during the DRL task. The magnitude of these associations was such that IRTs during the task decreased by 29-34% for every 1 SD increase in the corresponding blood PFC. CONCLUSIONS This study suggests an association between PFC exposure and childrens impulsivity. Although intriguing, there is a need for further investigation and replication with a larger sample of children.

Fish consumption, low-level mercury, lipids, and inflammatory markers in children

There is considerable evidence that consuming fish has numerous health benefits, including a reduced risk of cardiovascular disease. However, fish is also the primary source of human exposure to mercury (Hg). In a cross-sectional study of 9-11 year old children (N=100), we measured fish consumption, blood lipids, total blood Hg, diurnal salivary cortisol (4 samples collected throughout the day), and performed a proteomic analysis of serum proteins using spectral count shotgun proteomics. Children who consumed fish had a significantly more atheroprotective lipid profile but higher levels of blood Hg relative to children that did not consume fish. Although the levels of blood Hg were very low in these children (M=0.77 μg/L; all but 1 participant had levels below 3.27 μg/L), increasing blood Hg was significantly associated with blunted diurnal cortisol levels. Blood Hg was also significantly associated with acute-phase proteins suggesting systemic inflammation, and several of these proteins were found to significantly reduce the association between Hg and diminished cortisol when included in the model. This study of a pediatric population is the first to document an association between blood Hg, systemic inflammation, and endocrine disruption in humans. Without a better understanding of the long-term consequences of an atheroprotective lipid profile relative to blunted diurnal cortisol and systemic inflammation, a determination of the risk-benefit ratio for fish consumption by children is not possible.

Low-level Pb and cardiovascular responses to acute stress in children: The role of cardiac autonomic regulation

OBJECTIVE A number of studies suggest that Pb exposure increases cardiovascular disease risk in humans. As a potential mechanism for this effect, we recently reported a significant association between early childhood Pb levels and cardiovascular response to acute stress. The current study considers the association between current Pb levels and the autonomic nervous system activation pattern underlying the cardiovascular response to stress in a new cohort of children. METHODS We assessed blood Pb levels as well as cardiovascular responses to acute stress in 9-11 year old children (N=140). Sympathetic activation (measured with pre-ejection period) and parasympathetic activation (measured with high frequency heart rate variability) were also assessed. RESULTS In a sample with very low levels of blood Pb (M=1.0 μg/dL), we found that increasing blood Pb was associated with coinhibition of sympathetic and parasympathetic activation in response to acute stress. In addition, increasing Pb levels were associated with the hemodynamic stress response pattern typical of coinhibition--significantly greater vascular resistance and reduced stroke volume and cardiac output. CONCLUSIONS Blood Pb levels were associated with significant autonomic and cardiovascular dysregulation in response to acute psychological stress in children. Moreover, these effects were significant at Pb levels considered to be very low and notably well below the 10 μg/dL, the Centers for Disease Control and Prevention definition of an elevated blood Pb level. The potential for autonomic dysregulation at levels of Pb typical for many US children would suggest potentially broad public health ramifications.

Background lead and mercury exposures: Psychological and behavioral problems in children

Background The potential harm from exposure to nonessential metals, particularly mercury (Hg) and lead (Pb), has been the focus of research for years. Initial interest focused on relatively high exposures; however, recent evidence suggests that even background exposures might have adverse consequences for child development. Identifying the extent of these consequences is now a priority. Methods We assessed blood Pb and Hg levels in a biracial sample of 9–11 year‐old children (N = 203). Neurodevelopment and psychological functioning assessments included hostility, disruptive behaviors, emotion regulation, and autism spectrum disorder behaviors. Parasympathetic (vagal) responses to acute stress were indexed by heart rate variability (HRV) at rest and during stress. Results With increasing Pb levels, children exhibit higher levels of hostile distrust and oppositional defiant behaviors, were more dissatisfied and uncertain about their emotions, and had difficulties with communication. These significant associations were found within a range of blood Pb levels from 0.19 to 3.25 &mgr;g/dL, well below the “reference value” for children of >5 &mgr;g/dL. Vagal reactivity interacted with Hg such that increasing Hg was associated with increasing autism spectrum behaviors for those children with sustained vagal tone during acute stress. Conclusions This study is the first to demonstrate an association between very low‐level Pb exposure and fundamental psychological mechanisms that might explain prior associations with more complex outcomes such as delinquency. Analyses of vagal reactivity yielded entirely novel associations suggesting that Hg may increase autism spectrum behaviors in children with sustained vagal tone during acute stress. The novelty of these later findings requires additional research for confirmation and the cross‐sectional nature of the data caution against assumptions of causality without further research. HighlightsPb and Hg, psychological outcomes, and vagal responses were measured in children.Pb levels were associated with hostility, ODD, and poor emotional regulation.Hg was associated with autism spectrum for those with sustained vagal tone.

Low-level mercury in children: Associations with sleep duration and cytokines TNF-α and IL-6

There is a sizeable literature suggesting that mercury (Hg) exposure affects cytokine levels in humans. In addition to their signaling role in the immune system, some cytokines are also integrally associated with sleep behavior. In this cross-sectional study of 9-11 year old children (N=100), we measured total blood Hg in whole blood, serum levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), and objectively measured sleep and activity using actigraphy. Increasing blood Hg was associated with significantly shorter sleep duration and lower levels of TNF-α. IL-6 was not associated with sleep or blood Hg. This study is the first to document an association between total blood Hg and sleep (albeit a small effect), and the first to consider the associations of total blood Hg with cytokines TNF-α and IL-6 in a pediatric sample. Further research using alternative designs (e.g., time-series) is necessary to determine if there is a causal pathway linking low-level Hg exposure to sleep restriction and reduced cytokines.

Plasma prekallikrein levels are positively associated with circulating lipid levels and the metabolic syndrome in children.

Plasma prekallikrein (PK) has been shown to be associated with cardiovascular disease (CVD) and its risk factors, but these associations have not been investigated in children. The present study examined PK activity in relation to well-established cardiovascular risk factors in a cohort of children aged 9-11 years (N=97). We found a significant and positive association between PK and fasting levels of total cholesterol (p<0.01), non-high-density lipoprotein cholesterol (p<0.01), and triglycerides (p<0.001). In addition, there was a significant association between PK activity and the metabolic syndrome, a clustering of risk factors considered to have an impact on atherosclerosis and CVD mortality. Finally, we found that children with a family history of CVD had significantly elevated PK activity. These novel findings warrant further investigations into the relationship between circulating PK levels and CVD risk factors because PK may be involved in the progression of the disease state.

Accelerometer-determined physical activity and the cardiovascular response to mental stress in children

OBJECTIVES Cardiovascular reactivity has been associated with future hypertension and cardiovascular mortality. Higher physical activity (PA) has been associated with lower cardiovascular reactivity in adults, but little data is available in children. The purpose of this study was to examine the relationship between PA and cardiovascular reactivity to mental stress in children. DESIGN Cross-sectional study. METHODS This study sample included children from the Oswego Lead Study (n=79, 46% female, 9-11 years old). Impedance cardiography was performed while children participated in a stress response protocol. Children were also asked to wear Actigraph accelerometers on their wrists for 3 days to measure intensity and duration of PA and sedentary time. RESULTS In multivariable models, moderate to vigorous (MV) PA was associated with lower body mass index (BMI) percentile and lower total peripheral resistance (TPR) response to stress (beta=-0.025, p=0.02; beta=-0.009, p=0.05). After additional adjustment for BMI, MVPA was also associated with lower diastolic blood pressure response to stress (beta=-0.01, p=0.03). Total PA and sedentary time were not associated with BMI or cardiovascular responses to stress. CONCLUSIONS A modest, inverse relation of PA to vascular reactivity to mental stress was observed in children. These data provide confirmatory evidence that the promotion of PA recommendations for children are important for cardiovascular health.

The development and initial validation of the child perceived discrimination questionnaire

ABSTRACT Perceived discrimination can affect psychological and physical health, starting in childhood. Yet, the measures that exist for measuring perceived discrimination among children have methodological limitations and structural/theoretical inconsistencies. The Child Perceived Discrimination Questionnaire (CPDQ) fills the gaps in the current measures by assessing two dimensions of everyday discrimination from both child and adult sources. To assess the reliability and validity of the CPDQ, we examined data from 163 participants, aged 9–11 years, 52.15% female, 57.67% Black. Results indicated that the CPDQ has good to excellent internal consistency and provided preliminary support for an a priori hypothesized factor structure. The CPDQ also discriminated between different race groups and demonstrated construct validity. Future research should seek additional evidence of reliability and validity for the CPDQ, though this preliminary evidence suggests that the CPDQ is appropriate for assessing perceived discrimination in children.